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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 1840-1847
Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic
Indicators in Chronic Lymphocytic Leukemia
Rajendra N. Damle,
Tarun Wasil,
Franco Fais,
Fabio Ghiotto,
Angelo Valetto,
Steven L. Allen,
Aby Buchbinder,
Daniel Budman,
Klaus Dittmar,
Jonathan Kolitz,
Stuart M. Lichtman,
Philip Schulman,
Vincent P. Vinciguerra,
Kanti R. Rai,
Manlio Ferrarini, and
Nicholas Chiorazzi
From the Department of Medicine, North Shore University Hospital and
NYU School of Medicine, Manhasset, NY; the Department of Medicine, Long
Island Jewish Medical Center and the Albert Einstein College of
Medicine, New Hyde Park, NY; and the Division of Clinical Immunology,
Istituto Nazionale per la Ricerca sul Cancro, Dipartmento Oncologia
Clinica e Sperimentale, Universita di Genova, Genova, Italy.
Cellular immunophenotypic studies were performed on a cohort of
randomly selected IgM+ B-chronic lymphocytic leukemia
(B-CLL) cases for which Ig VH and VL gene
sequences were available. The cases were categorized based on V gene
mutation status and CD38 expression and analyzed for treatment history
and survival. The B-CLL cases could be divided into 2 groups. Those
patients with unmutated V genes displayed higher percentages of
CD38+ B-CLL cells ( 30%) than those with mutated V
genes that had lower percentages of CD38+ cells
(<30%). Patients in both the unmutated and the 30%
CD38+ groups responded poorly to continuous multiregimen
chemotherapy (including fludarabine) and had shorter survival. In
contrast, the mutated and the <30% CD38+ groups
required minimal or no chemotherapy and had prolonged survival. These
observations were true also for those patients who stratified to the
Rai intermediate risk category. In the mutated and the <30%
CD38+ groups, males and females were virtually equally
distributed, whereas in the unmutated and the 30%
CD38+ groups, a marked male predominance was found. Thus,
Ig V gene mutation status and the percentages of CD38+
B-CLL cells appear to be accurate predictors of clinical outcome in
B-CLL patients. These parameters, especially CD38 expression that can
be analyzed conveniently in most clinical laboratories, should be
valuable adjuncts to the present staging systems for predicting the
clinical course in individual B-CLL cases. Future evaluations of new
therapeutic strategies and drugs should take into account the different
natural histories of patients categorized in these manners.
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